The apparent increase in adrenergic activity observed in the organism in the hyperthyroid state in the presence of a normal level of circulating catecholamines may result from enhanced responsiveness to basal or threshold concentrations of catecholamines. This may result from an increase in the number of beta-receptors demonstrated recently. The purpose of the present study was to measure the cAMP-dependent protein kinase activation and contractile response subsequent to threshold levels of beta-stimulation with isoproterenol in the hyperthyroid and euthyroid heart. In addition, since the response to catecholamines is mediated by an increase in transsarcolemmal Ca2 ion influx this was monitored via transmembrane action potential measurements in the hyperthyroid and euthyroid hearts.